The long-term objectives of our research program are to clarify the central mechanisms underlying acute and chronic dental and orofacial pain and its control. Our recent NIH-supported research has resulted in major new insights into the neuroplasticity of the trigeminal (V) brainstem complex, and into brainstem mechanisms underlying deep (e.g. muscle; and temporomandibular joint, TMJ) as well as cutaneous (facial) pain. THE EXPRESSION OF NEUROPLASTICITY THAT WE DOCUMENTED IN THE ADULT v BRAINSTEM COMPLEX WAS REVEALED BY ENDODONTIC DEAFFERENTATION OF THE TOOTH PULP. IN THE SPINAL SOMATOSENSORY SYSTEM, PERIPHERAL DEAFFERENTATION CAN ALSO INDUCE ALTERATIONS IN SOMATOSENSORY PATHWAYS THAT HAVE BEEN VIEWED AS A REFLECTION OF CNS NEUROPLASTICITY AND AS PROCESSES CONTRIBUTING TO THE DEVELOPMENT OF CHRONIC PAIN. THE MECHANISMS AS PROCESSES CONTRIBUTING TO THE DEVELOPMENT OF CHRONIC PAIN. THE MECHANISMS UNDERLYING THESE CHANGES IN INHIBITION OF EXISTING AFFERENT INPUTS. OUR STUDIES OF V BRAINSTEM CELLS INDICATED THAT MAXILLARY OR MANDIBULAR PULP DEAFFERENTATION IN ADULT ANIMALS RESULTED IN STATISTICALLY SIGNIFICANT ALTERATIONS IN MECHANORECEPTIVE FIELD AND RESPONSE PROPERTIES THAT WERE ESPECIALLY APPARENT IN ORALS NEURONS; THESE EFFECTS WERE SIGNIFICANTLY PROLONGED WITH MORE EXTENSIVE PULP DEAFFERENTATION. AS FOR THE SPINAL SYSTEM, HOWEVER, the mechanisms underlying our documented physiological changes after deafferentation of the pulp are unclear. THEREFORE, we will test hypotheses that mandibular pulp deafferentation is associated with (A) SPROUTING OF MAXILLARY AFFERENTS INTO REGIONS OF V SUBNUCLEUS ORALIS NORMALLY DEVOTED TO THE REPRESENTATION OF THE MANDIBULAR DIVISION; (B) a decrease in afferent inhibition; and (C) a decrease in primary afferent depolarization (PAD) WHICH IS CONSIDERED A REFLECTION OF PRESYNAPTIC INHIBITION. Comparison of these features between normal and deafferented adult animals will be made in V brainstem neurons or primary afferents IN QUANTITATIVE ANALYSES UTILIZING, FOR HYPOTHESES B & C, OUR WELL-DOCUMENTED EXPERTISE IN EXTRACELLULAR SINGLE UNIT RECORDING. TO ADDRESS HYPOTHESIS A, NEW APPROACHES FOR OUR LAB INVOLVING HRP LABELLING OF V NERVE BRANCHES AND INTRACELLULAR HRP LABELLING OF PHYSIOLOGICALLY IDENTIFIED SINGLE UNITS WILL BE USED. THESE STUDIES WILL CLARIFY SOME OF THE MECHANISMS THAT MAY BE INVOLVED IN NEUROPLASTIC RESPONSES OF THE V BRAINSTEM COMPLEX TO INJURY OF THE TOOTH PULP AND THAT MAY UNDERLIE THE DEVELOPMENT OF CHRONIC OROFACIAL PAIN.